We will utilize a number of different viral and non-viral systems to elucidate the mechanism(s) by which proto-oncogenes become activated, and to ascertain their role in the malignant cell. Systems to be studied will include: (a) ALV-induced lymphomas; (b) RPV-induced fibrosarcomas; (c) rapidly-appearing angiosarcomas and lymphomas induced by RPV, or by RPV/ALV recombinants; (d) Burkitt lymphoma; (e) human chronic myelogenous leukemia. Efforts will be made to determine the role of the myc gene product in normal and transformed cells, and to identify sequences and second-site genes responsible for control of its expression. We will also attempt to identify "new" oncogenes involved in RPV-induced fibrosarcomas, and in various stages of tumor progression in chronic myelogenous leukemia.